PRESCRIBING INFORMATION (PI)

BOTOX^® (Botulinum toxin type A (from Clostridium botulinum))

Refer to Summary of Product Characteristics (SmPC) for full information before prescribing.

PRESENTATION:  50, 100 & 200 Allergan Units/vial.  Powder for solution for Injection.

INDICATIONS: Management of symptomatic relief of blepharospasm, hemifacial spasm and idiopathic cervical dystonia (spasmodic torticollis). Management of severe hyperhidrosis of the axillae, which does not respond to topical treatment with antiperspirants or antihidrotics. Prophylaxis of headaches in adults with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine). Management of bladder dysfunctions in adult patients who are not adequately managed with anticholinergics: overactive bladder with symptoms of urinary incontinence, urgency and frequency; neurogenic detrusor overactivity with urinary incontinence due to subcervical spinal cord injury (traumatic or non-traumatic), or multiple sclerosis. Focal spasticity: for the symptomatic treatment of focal spasticity including elbow, wrist, hand in paediatric cerebral palsy patients, two years of age or older as an adjunct to rehabilitative therapy; ankle and foot in ambulant paediatric cerebral palsy patients, two years of age or older as an adjunct to rehabilitation therapy; upper limb spasticity in adults; ankle and foot disability due to lower limb spasticity in adults.

DOSAGE AND ADMINISTRATION: See Summary of Product Characteristics for full information. Botulinum toxin Units are not interchangeable from one product to another. BOTOX must only be reconstituted with sterile sodium chloride 9 mg/ml (0.9%) solution for injection. Single use only; unused solution to be discarded. If different vial sizes of BOTOX are being used as part of one injection procedure, care should be taken to use the correct amount of diluent when reconstituting a particular number of units per 0.1 ml. The amount of diluent varies between BOTOX 50, 100 and 200 Allergan Units.  Each syringe should be labelled accordingly. Refer to specific guidelines for each indication below. In the event of treatment failure or diminished effect following repeat injections, alternative treatment methods should be employed. Blepharospasm: Inject using a sterile 27–30 gauge/0.40-0.30 mm needle. Initially, inject 1.25–2.5 Units (0.05-0.1ml at each site) into the medial and lateral orbicularis oculi of the upper lid and the lateral orbicularis oculi of the lower lid. At repeat treatment sessions, dose may be increased up to two-fold. Initial dose should not exceed 25 Units per eye. Total dose should not exceed 100 Units every 12 weeks. Hemifacial spasm: Treat as for unilateral blepharospasm (as above). Cervical dystonia: Inject using a 25, 27 or 30 gauge/0.50-0.30 mm needle (for superficial muscles) or 22 gauge (deeper musculature). Tailor dosing to individual patient based on the head and neck position, location of pain, muscle hypertrophy, body weight and response. Do not inject sternocleidomastoid muscle bilaterally. No more than 50 Units should be given at any one injection site. No more than 100 Units should be given to the sternomastoid. Total dose should not exceed 200 Units for first course of therapy. A total dose of 300 Units at any one sitting should not be exceeded. Primary hyperhidrosis of the axillae: Inject using a 30 gauge needle. Recommended injection volume 0.1-0.2 ml. Inject 50 Units intradermally to each axilla, evenly distributed in multiple sites 1-2 cm apart. Injections should not be repeated more frequently than every 16 weeks. Paediatric cerebral palsy focal upper and lower limb spasticity: Appropriately sized sterile needle. Needle length should be determined based on muscle location and depth. Localisation of the involved muscles with techniques such as needle electromyographic guidance, nerve stimulation, or ultrasound is recommended. Prior to injection, local anaesthesia or local anaesthesia in combination with minimal or moderate sedation may be used, per local site practice. The safety and efficacy of BOTOX in the treatment of paediatric spasticity has not been evaluated under general anaesthesia or deep sedation/analgesia.  The recommended dose for treating paediatric upper limb spasticity is 3 Units/kg to 6 Units/kg body weight divided among the affected muscles. The total dose of BOTOX administered per treatment session in the upper limb should not exceed 6 Units/kg body weight or 200 Units, whichever is lower. The recommended dose for paediatric lower limb spasticity is 4 Units/kg to 8 Units/kg body weight divided among the affected muscles. The total dose of BOTOX administered per treatment session in the lower limb should not exceed 8 Units/kg body weight or 300 Units, whichever is lower. When treating both lower limbs or the upper and lower limbs in combination, the total dose should not exceed the lower of 10 Units/kg body weight or 340 Units, in a 12-week interval. If it is deemed appropriate by the treating physician, the patient should be considered for re-injection when the clinical effect of the previous injection has diminished, no sooner than 12 weeks after the previous injection. Focal upper limb spasticity in adults: Inject using a 25, 27 or 30 gauge needle. Determine needle length based on muscle location and depth. Tailor dose and number of sites based on size, number and location of muscles involved, severity of spasticity, the presence of local muscle weakness and treatment response. Total dose 400 Units, divided among selected muscles. Focal lower limb spasticity in adults: Inject using a 25, 27 or 30 gauge needle. Needle length should be determined based on muscle location and depth. 300 units to 400 units divided among up to 6 muscles. Chronic Migraine: Inject using 30 gauge, 0.5 inch needle, or 1 inch needle for thicker muscles in neck region if required. Inject 0.1ml (5 Units) intramuscularly to 31 (up to 39) injection sites, divided across seven specific head/neck muscle areas including frontalis, corrugator, procerus, occipitalis, temporalis, trapezius and cervical paraspinal muscles. Inject bilaterally, with the exception of procerus. Total dose 155 Units-195 Units. Overactive Bladder: Inject via a flexible or rigid cystoscope, avoiding the trigone and base. The recommended dose is 100 Units of BOTOX, as 0.5 ml (5 Units) injections across 20 sites in the detrusor muscle. Neurogenic Detrusor Overactivity: lnject using a flexible or rigid cystoscope, avoiding the trigone and base. The recommended dose is 200 Units of BOTOX, as 1 ml (~6.7 Units) injections across 30 sites in the detrusor muscle. When treating adult patients for multiple indications, the maximum cumulative dose should not exceed 400 units in a 12-week interval. In treating paediatric patients, including when treating for multiple indications, the maximum cumulative dose should not exceed the lower of 10 Units/kg body weight or 340 Units, in a 12-week interval.

CONTRAINDICATIONS: Known hypersensitivity to any constituent.  Presence of infection at proposed injection site(s). For the management of bladder dysfunctions: urinary tract infection at the time of treatment; acute urinary retention at the time of treatment (in patients who are not routinely catheterising); patients who are not willing and/or able to initiate catheterisation post-treatment if required; presence of bladder calculi.

SPECIAL WARNINGS AND PRECAUTIONS: The recommended dosages and frequencies of administration of BOTOX should not be exceeded due to the potential for overdose, exaggerated muscle weakness, distant spread of toxin and the formation of neutralizing antibodies.  Initial dosing in treatment naive patients should begin with the lowest recommended dose for the specific indication. Prescribers and patients should be aware that side effects can occur despite previous injections being well tolerated. There are reports of side effects related to spread of toxin distant from injection site, sometimes resulting in death. The risk of symptoms is probably greatest in patients who have underlying conditions and comorbidities, including children and adults treated for spasticity, and are treated with high doses. Elderly and debilitated patients should be treated with caution. Dysphagia has also been reported following injection to sites other than the cervical musculature. Extreme caution in patients with underlying defective neuromuscular transmission/neurological disorder/peripheral motor neuropathic diseases and history of dysphagia and aspiration. Patients should seek medical help if swallowing, speech or respiratory disorders arise. Previously sedentary patients should resume activities gradually. Relevant anatomy and changes due to prior surgical procedures must be understood prior to administration and injection into vulnerable anatomic structures must be avoided. Pneumothorax associated with injection procedure has been reported. Serious adverse events including fatal outcomes have been reported in patients who had received off-label injections directly into salivary glands, the oro-lingual-pharyngeal region, oesophagus and stomach.  If serious and/or immediate hypersensitivity reactions occur (in rare cases), injection of toxin should be discontinued and appropriate medical therapy, such as epinephrine, immediately instituted. Procedure related injury could occur. Caution in the presence of inflammation at injection site(s) or when excessive weakness/atrophy is present in target muscle. Reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. New onset or recurrent seizure occurred rarely in predisposed patients, however relationship to botulinum toxin has not been established. Clinical fluctuations may occur during repeated use.  Too frequent or excessive dosing can lead to antibody formation and reduced effectiveness. Paediatric use: The safety and efficacy of BOTOX in indications other than those described for the paediatric population in the Summary of Product Characteristics, have not been established. Use extreme caution in paediatric patients with neurologic debility, dysphagia, recent history of aspiration pneumonia or lung disease. Very rare reports of possible distant spread of toxin in paediatric patients with co-morbidities, predominantly with cerebral palsy. Blepharospasm: Reduced blinking following injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid areas to avoid ectropion, and vigorous treatment of any epithelial defect should be employed.  Ecchymosis and facial swelling can occur. Caution when treating patients at risk for angle closure glaucoma.  Cervical Dystonia: Possibility of dysphagia which may be mild but could be severe. Limiting dose into the sternocleidomastoid muscle to less than 100 Units may decrease the risk of dysphagia. Focal spasticity: Not intended as a replacement for the usual standard of care regimens.  Not likely to be effective in improving range of motion at a joint affected by a fixed contracture. Caution in those who may be at an increased risk of fall. Hyperhidrosis of the axillae: Exclude secondary causes of hyperhidrosis to avoid symptomatic treatment without the diagnosis and/or treatment of underlying disease. Chronic Migraine: Efficacy has not been shown in prophylaxis of episodic migraine (headaches <15 days per month). Bladder Dysfunctions: Prophylactic antibiotics should be administered to patients with sterile urine or asymptomatic bacteriuria. The decision to discontinue anti-platelet therapy should be subject to local guidance and benefit/risk consideration for the individual patient. Patients on anti-coagulant therapy need to be managed appropriately to decrease the risk of bleeding. Observe patient for at least 30 minutes post-injection. In patients who are not regularly practicing catheterisation, post-void residual urine volume should be assessed within 2 weeks post-treatment and periodically as medically appropriate. Instruct patients to contact their physician if they experience difficulties in voiding as catheterisation may be required. Overactive Bladder: If a local anaesthetic intravesical instillation is performed, the bladder should be drained and rinsed with sterile saline before the next steps of the injection procedure. Neurogenic Detrusor Overactivity: Autonomic dysreflexia associated with the procedure can occur.

INTERACTIONS: Theoretically, effect may be potentiated by aminoglycoside antibiotics or other drugs that interfere with neuromuscular transmission.

PREGNANCY AND LACTATION: Pregnancy: BOTOX is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding: There is no information on whether BOTOX is excreted in human milk.  The use of BOTOX during breast-feeding cannot be recommended. Fertility: There are no adequate data on the effects on fertility from the use of botulinum toxin type A in women of childbearing potential. Studies in male and female rats have shown fertility reductions.

DRIVING: May cause asthenia, muscle weakness, somnolence, dizziness and visual disturbance which could affect driving and operation of machinery.

ADVERSE REACTIONS: See Summary of Product Characteristics for full information on adverse reactions. Common and serious adverse reactions are included here. Adverse events usually occur within the first few days following injection and are generally transient, but may persist for several months or, rarely, longer.  Local muscle weakness represents the expected pharmacological action. Localised pain, tenderness and/or bruising may be associated with the injection. Fever and flu syndrome have been reported.

Blepharospasm/Hemifacial Spasm – very common: eyelid ptosis; common: punctate keratitis, lagophthalmos, dry eye, photophobia, eye irritation and lacrimation increase, ecchymosis, irritation, face oedema; uncommon: dizziness, facial paresis, facial palsy, keratitis, ectropion, diplopia, entropion, visual disturbance and vision blurred, rash/dermatitis, fatigue; rare: eyelid oedema; very rare: corneal ulceration, corneal epithelium defect, corneal perforation.  Cervical Dystonia – very common: dysphagia, muscular weakness, pain; common: rhinitis, upper respiratory tract infection, dizziness, hypertonia, hypoaesthesia, somnolence, headache, dry mouth, nausea, musculoskeletal stiffness and musculoskeletal soreness, asthenia, influenza-like illness, malaise; uncommon: diplopia, eyelid ptosis, dyspnoea, dysphonia, pyrexia.  Focal spasticity of the upper limb in paediatric patients – Common: upper respiratory tract infection, nausea, muscular weakness, injection site pain. Focal spasticity of lower limb in paediatric patients – Common: rash, injection site pain, gait disturbance, ligament sprain, skin abrasion.  Focal upper limb spasticity in adult patients – Common: nausea, pain in extremity, muscular weakness, fatigue, peripheral oedema.  Focal lower limb spasticity in adult patients – Common: rash, arthralgia, musculoskeletal stiffness, muscular weakness, peripheral oedema, fall.  Primary hyperhidrosis of the axillae – Very common: injection site pain; Common: headache, paraesthesia, hot flushes, hyperhidrosis (non axillary sweating), abnormal skin odour, pruritus, subcutaneous nodule, alopecia, pain in extremity, pain, injection site oedema, injection site haemorrhage, injection site hypersensitivity, injection site irritation, asthenia, injection site reactions; Uncommon: nausea, muscular weakness, myalgia, arthropathy.  Chronic migraine – Common: headache, migraine including worsening of migraine, facial paresis, eyelid ptosis, pruritus, rash, neck pain, myalgia, musculoskeletal pain, muscle spasms, muscle tightness, muscular weakness, injection site pain; uncommon: eyelid oedema, dysphagia, pain of skin, pain in jaw.  Overactive bladder – Very common: urinary tract infection, dysuria; Common: bacteriuria, urinary retention, pollakiuria, leukocyturia, residual urine volume.  Adult urinary incontinence due to neurogenic detrusor overactivity – Very common: urinary tract infection, bacteriuria, residual urine volume, urinary retention; Common: insomnia, constipation, muscular weakness, muscle spasm, haematuria, bladder diverticulum, dysuria, fatigue, gait disturbance, autonomic dysreflexia, fall. Paediatric neurogenic detrusor overactivity – Very common: bacteriuria; Common: urinary tract infection, leukocyturia, haematuria.

LEGAL CLASSIFICATION: POM

MARKETING AUTHORISATION NUMBERS/PRESENTATIONS/NHS LIST PRICE:

Marketing Authorisation Number: 50 Units: PL 41042/0059, 100 Units: PL 41042/0057, 200 Units: PL 41042/0058

Basic NHS Price: 50 Units: £77.50, 100 Units: £138.20, 200 Units £276.40.

FURTHER INFORMATION: available from: AbbVie Ltd, Maidenhead, Berkshire, SL6 4UB.

DATE OF REVISION: April 2023

UK-PI-BOTOX-Tx 04

Date of preparation: June 2023. UK-BTX-230074.